Chiral syntheses of the antibiotics anisomycin and pentenomycin from carbohydrates

Abstract

-Syntheses of the natural, optically active forms of the antibiotics anisomycin and pentenomycin are described using simple glucose derivatives as chiral starting materials. The key step in the synthesis of anisomycin is the formation of a pyrrolidine ring embodying all three of the desired asymmetric centers via intramolecular nucleophilic displacement of a 3-Q-tosyl function in an-;ppropriately substituted 6-amino-6-deoxy-ß-~-talofuranose derivative. Further elaboration involves the liberation of an aldehyde group by periodate oxidation of the 1,2-diol, Grignard coupling and removal of extraneous functions and blocking groups by several reductive steps.The syntheses of pentenomycin, and its simpler analog 6-deoxypentenomycin, proceed via conversion of 3-benzyloxymethyl and 3-methyl derivatives of 1,2:5,6-di-Q-isopropylidene-a-Q-allofuranose, respectively, into the respective 3-substituted methyT 2,3-cycloalkylidene-5-deoxy-Q-erythro-pent-4-enofuranosides. Acidic hydrolysis of the latter gives the-related 4-ketoaldehydes that undergo intramolecular aldol condensations to form the appropriately substituted 2-cyclopenten-1-ones that can be converted into the target compounds.It is axiomatic in organic chemistry that the synthesis of an optically active product must make use of chiral substances, either as resolving agents or as synthetic intermediates. From the point of view of overall efficiency, the use of an appropriate chiral starting material is of particular attraction. This approach has found extensive use over the years, and syntheses of a great variety of optically active natural products have been described starting from readily available chiral substances such as amino acids and simple terpenes (Ref. 1). In spite of the fact that carbohydrates constitute one of Nature's richest sources of chirality, only in recent years have these substances found wide use as starting materials for asymmetric syntheses. This stems, to a considerable degree, from a lang standing aversion an the part of many organic chemists to work with carbohydrates, which were considered to be mainly intractable syrups. With the advent of improved and more selective protecting groups and, in particular, the extensive application of contemporary instrumental analysis, carbohydrate chemistry is now enjoying a new image. As synthetic intermediates, carbohydrates are now becoming recognized as readily available, polyfunctional molecules containing several sites of predictably controllable asymmetry. In recent years this has led to the use of carbohydrate derivatives as intermediates in the synthesis of a nurober of optically active natural products of widely divergent structures. Hanessian and Raucourt (Ref. 6). In the present paper we further extend this general approach through a description of the syntheses of two optically active antibiotics, anisomycin (1) and pentenomycin (2), starting from ~-glucose.--Anisomycin (1) was isolated from two strains of Streptomyces by Sobin and Tanner of Chas. (Refs. l7, 18) have also prepa...

Chiral deuteration at C-5 of 1,5-anhydropentofuranose derivatives.

“…Compound4 was prepared by a new method different from the one reported.5'6) Periodate oxidation of 1-0benzoyl-2,3-O-isopropylidene-a-D-mannofuranose (8),7) followed by reduction of the resulting aldehyde with sodium borohydride, gave l-0-benzoyl-2,3-0-isopropylidene-a-D-lyxofuranose (9) in an 89% yield. p-To\uenesulfonylation of 9 gave a 5-0-tosylate (10) in a 90%yield, which was then treated with sodium hydride (NaH) in Af,A/-dimethyl-formamide (DMF) to give crystalline 4 in an 83% yield.…”

Chiral Deuteration at C-5 of 1,5-Anhydropentofuranose Derivatives

“…5 ,6) Periodate oxidation of 1-0-benzoyl-2,3-0-isopropylidene-a-D-mannofuranose (8), 7) followed by reduction of the resulting aldehyde with sodium borohydride, gave 1-0-benzoyl-2,3-0-isopropylidene-a-D-lyxofuranose (9) in an 89% yield. p-Toluenesulfonylaticn of 9 gave a 5-0-tosylate (10) in a 90% yield, which was then treated with sodium hydride (NaH) in N,N-dimethyl-formamide (DMF) to give crystalline 4 in an 83% yield.…”

Readily Available Chiral Carbon Fragments and Their Use in Synthesis

“…Three syntheses of this compound in chiral form have been reported (351)(352)(353)(354). An example of such an antibiotic is anisomycin (842).…”